Phosphonofluoridate inhibition of acetylcholinesterase: an exceptionally rapid reactant

Both isomers of 3.6-dioxa-(8-(2,4-dinitrophenoxy))octyl] methylphosphono-fluoridate (I) react rapidly with eel acetylcholinesterase. At pH 6.61 and 25°C, the reaction rate constants for the fast and slow isomers are 3 × 10⁹ and 5 × 10⁷M^?1 min^?1. Despite the very high rate of reaction with acetylcholinesterase, which for the fast isomer is approximately 40 times that of sarin, the toxicity of I is only $\text{1}\text{9}$ that of sarin. Enzyme inhibited by I is resistant to reactivation by TMB-4.